The senior investigators supported by this program propose a variety of studies for the coming year. 1) Studies on serum complement will attempt to: a) determine the chemical denominator of substances that activate the alternative pathway, b) explore the topology of the subunits within the membrane attack pathway, c) investigate further the inhibition of cytotoxic lymphocytes by antibodies to complement, d) analyse the complement enzymes and their control mechanisms, and e) study the role of complement, particlarly the alternative pathway, in the inactivation and phagocytosis of bacteria. 2) Other studies on mediator mechanisms of immunologic injury will include: a) study of the participation of the Hageman factor system in spontaneous and experimentally induced animal diseases, b) analysis of mechanisms of degranulation of mast cells and the role of these mediator cells in murine immunopathologic responses to endotoxins, c) study of the in vivo fate and disappearance of low density forms of lipopolysaccharide molecules of different types and their relationship to associated pathology. 3) Work on the immunopathologic aspects of viral infections will include: a) studies on the nature of the immunologic attack on virus-infected cells as well as the mechanisms of virus persistence, latency and reactivation, b) development of hybridoma secreting antibodies specifically reactive with the various antigens of the viruses we are studying as well as the host gene production expressed on the infected cell surface. 4) Studies on the spontaneously occurring autoimmune murine diseases will continue with special emphasis on: a) the cause of the polyclonal B cell activation expressed early in the life of these animals, b) the nature of and pathogenic role played by the several cellular immune abnormalities observed in these mice and c) the nature and atherogenic potential of the degenerative, immunologically induced vascular lesions of these animals. 5) Studies on tolerance will be concerned with the cellular requirements for induction of immunologic tolerance including the activation of T and B cells and the sequence of events involved in either diferentiation or inactivation of B cell antibody formation. 6) Investigation of the immunopathology of immune-complex induced glomerulonephritis will emphasize the possible role of monocytes and macrophages in the mediation of glomerular injury.